Study of S-4321 in Participants With an Autoimmune or Immune-mediated Disease

Criteria the registry did not label

• All Participants Major Inclusion Criteria:
• Adult males and females, 18 to 75 years of age (inclusive)
• Body mass index (BMI) ≥18.0 and \<40.0 kg/m2 with a minimum body weight of 45 kg
• Use of adequate contraception for both males and females. Female volunteers must be of nonchildbearing potential or if of childbearing potential, must have a negative pregnancy test.
  • All Participants Major Exclusion Criteria:
• Have received a PD-1 agonist, immune checkpoint agonist, immune checkpoint inhibitor, anti-CD19 or anti-CD20 agents, cell therapy, B cell modulating agents, alkylating agents, or any other immune cell depleting therapy.
• Have received azathioprine, cyclosporine, mycophenolate mofetil, or tacrolimus within 4 weeks
• Unable or unwilling to discontinue a prohibited medication
• Presence of clinically relevant immunosuppression
• Current infection or history of severe infection
• Any history of malignant disease, with some exceptions
  • Major inclusion/exclusion for each autoimmune or immune-mediated disease:
  • For RA:
• Confirmed diagnosis of moderate to severe active RA by the American College of Rheumatology (ACR) 2010/European League Against Rheumatism (EULAR) criteria for at least 3 months prior to the Screening 1 visit, and:
  • ≥6 swollen joint count based on 66 joint count
  • ≥6 tender joint count based on 68 joint count
  • Seropositive for RF and/or ACPA
  • Elevated hsCRP ≥1.2 times greater than the ULN
  • Does not have Class IV RA according to ACR revised criteria
• Inadequate response to, or loss of response, or intolerance to:
  • \>1 conventional synthetic DMARD after 3 months of therapy OR
  • \>1 biologic DMARD/targeted synthetic DMARD after 3 months of therapy
  • Has not failed 3 or more bDMARDs and/or tsDMARDs
  • For PsA:
• Confirmed diagnosis of adult-onset PsA classified by the Classification Criteria for Psoriatic Arthritis (CASPAR) for at least 3 months prior to the Screening 1 visit, with all of the following:
  • Active PsO defined by at least 1 psoriasis lesion
  • Active disease defined by \>3 swollen joints and \>3 tender joints using the 76/78 swollen and tender joint count
• Received standard doses of NSAIDs for \>4 weeks or csDMARDs for \>3 months and has been on a stable dose for \>8 weeks, or participant has intolerance to NSAIDs or DMARDs
• Participants may be TNF inhibitor therapy naïve or may have received 1 prior TNF inhibitor
• Has not had inadequate response or intolerance to 2 or more bDMARDs or csDMARDs
  • For PsO:
• Confirmed diagnosis of moderate to severe plaque PsO for at least 6 months, with all of the following:
  • Psoriasis Area and Severity Index (PASI) \>12 points
  • Static Physician's Global Assessment (sPGA) \>3 points
  • Body surface area (BSA) of PsO involvement \>10%
• Cannot have a clinically significant flare within 12 weeks
• Does not have history of erythrodermic psoriasis, generalized or localized pustular psoriasis, predominantly guttate psoriasis, or medication-induced or medication-exacerbated psoriasis
• Has not had inadequate response to more than 2 prior bDMARDs
  • For CLE (with or without systemic manifestations):
• Histologically confirmed diagnosis of CLE with or without systemic manifestations for at least 6 months
• Has active skin manifestations as measured by CLASI-A \>10 or CLASI-A \>8, if there is no alopecia or mucous membrane lesions
• Participant must have an active CLE lesion despite an adequate trial of antimalarial treatment for at least 6 months.
• Cannot have active lupus nephritis or moderate-to-severe or chronic kidney disease with eGFR \<45 mL/min/1.73m2
• Cannot have active neuropsychiatric SLE
  • For AD:
• Confirmed diagnosis of AD as defined by the American Academy of Dermatology: Guidelines of Care for the Management of Atopic Dermatitis for at least 12 months
  • Eczema Area and Severity Index (EASI) \>16
  • Validated Investigator Global Assessment (vIGA-AD) \>3
  • BSA of AD involvement \>10%
  • PP-NRS) \>4 (average of daily scores) during the 7 days prior to dosing
• Inadequate response to existing topical medications within 6 months or has a history of intolerance to topical therapy as defined by at least 1 of the following:
  • Inability to achieve good disease control after use TCS for at least 4 weeks
  • Documented history of clinically significant AEs with the use of TCS
  • Failed systemic therapies intended to treat AD within 6 months
  • Additional inclusion/exclusion criteria will apply.